Pearce-Kelling S E, Aleman T S, Nickle A, Laties A M, Aguirre G D, Jacobson S G, Acland G M
Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Mol Vis. 2001 Feb 25;7:42-7.
D-cis-diltiazem, a calcium channel blocker, has been reported to enhance photoreceptor survival in the rd mouse, a model of retinitis pigmentosa (RP) resulting from mutation of the PDE6B gene. We tested the hypothesis that diltiazem treatment would similarly rescue the canine rcd1 model of RP, which is also caused by a null mutation in the PDE6B gene.
D-cis-diltiazem was delivered orally twice daily to rcd1 affected dogs beginning at 4 weeks of age; untreated age-matched rcd1 dogs served as controls. At 14 weeks, electroretinograms (ERG) were performed on all animals; 14 dogs were euthanized at this age, and 2 dogs at 25 weeks of age. Eyes were enucleated, fixed, and processed for routine histological examination.
No significant differences were found in ERG or histopathologic parameters between diltiazem-treated and untreated rcd1 dogs. Neither rcd1 group showed a rod b-wave; ERGs evoked by single white flashes (dark- or light-adapted) and flicker were also identical between groups. Similarly, treated and untreated animals did not differ in the degree of preservation of the photoreceptor layer, confirmed in cell counts within the outer nuclear layer.
Treatment of rcd1 affected dogs with D-cis-diltiazem did not modify the photoreceptor disease when results were assessed using either ERG or histopathologic criteria. The positive photoreceptor-rescue effect of calcium channel blockers reported in the rd mouse was thus not generalizable to another species with retinal degeneration due to mutation in the PDE6B gene. Caution needs to be exerted in extrapolation to the comparable human forms of RP.
D-顺式地尔硫䓬是一种钙通道阻滞剂，据报道它能提高rd小鼠（一种因PDE6B基因突变导致的视网膜色素变性（RP）模型）中光感受器的存活率。我们检验了这样一个假设，即地尔硫䓬治疗同样能挽救犬类rcd1 RP模型，该模型也是由PDE6B基因的无效突变引起的。
从4周龄开始，每天给受rcd1影响的犬口服两次D-顺式地尔硫䓬；年龄匹配的未治疗的rcd1犬作为对照。在14周时，对所有动物进行视网膜电图（ERG）检查；在这个年龄安乐死14只犬，在25周龄时安乐死2只犬。摘除眼球，固定并进行常规组织学检查。
地尔硫䓬治疗组和未治疗组的rcd1犬在ERG或组织病理学参数上没有发现显著差异。两个rcd1组均未显示出视杆细胞b波；两组之间单次白色闪光（暗适应或明适应）和闪烁诱发的ERG也相同。同样，治疗组和未治疗组动物在光感受器层的保存程度上没有差异，这在外核层的细胞计数中得到证实。
当使用ERG或组织病理学标准评估结果时，用D-顺式地尔硫䓬治疗受rcd1影响的犬并没有改变光感受器疾病。因此，rd小鼠中报道的钙通道阻滞剂对光感受器的挽救作用不能推广到另一种因PDE6B基因突变导致视网膜变性的物种。在推断到类似的人类RP形式时需要谨慎。
